The long-term goal of the proposed work is to determine the biological functions of the glycosyl moieties of cell-surface and extracellular glycosylated proteins. In particular, we plan to combine the powerful serology, genetics and quantitative bioassays, provided by cellular immunology, with the recent biochemical advances in the biosynthesis and structures of cell surface glycosyl moieties to determine the involvement of complex saccharides in cell-mediated immunity. Currently, we are conducting detailed analyses of complex glycosaminoglycans and glycopeptides in developing murine thymocytes and thymic epithelium. In addition, we are using specific inhibitors of glycosylation and stimulators of glycosaminoglycan synthesis, in conjuction with mixed lymphocyte reaction and cell-mediated cytotoxicity assays, to ascertain the involvement of these cell-surface saccharides in immune cellular interactions. Both the biochemical and biological affects of the drugs are being investigated. The effects of mitogens and allogenic stimulation on lymphocyte glycosaminoglycan metabolism is also under investigation. Our recent studies strongly support the notion that cell-surface glycosyl moieties, including glycosaminoglycans and Asn-linked saccharides, are involved in the cell-mediated immune reactions mediated by thymic lymphocytes. Our future efforts are focused on providing the biochemical basis of their roles in cellular interactions.